Improving risk stratification and early detection

of Hepatocellular Carcinoma in Africa

Cairo Sep 2019

Ashraf Omar M,D

Prof Hepatology and Endemic Medicine

Cairo University

Head of the Egyptian Society Of Liver

Cancer (ESLC)

Head of MENA NCCN Committee for HCC

• Disclosure

Nothing to disclose

• HCC is a major health problem in Africa

• It is a major cause of premature death in Africa (chronic HBV)

• Risk factors are well known and avoidable in most cases.

HCC In Africa

• Fourth most common cancer in both genders.

• Burden :64,779 new cases , 63,562 d. ..incidence matches mortality rate : 0.9

• Prevalence of about 56,736 cases in 2018.

• In men, it is the second most common cancer and the second cause of death due to cancer.

• Socioeconomic : Rural>>Urban

Ferlay J et al , global Cancer Observatory 2018Lancet 2016;388

MORTALITY

INCIDENCE

Ferlay J et al , global Cancer Observatory 2018

Incidence and Mortality

• Depending on the region, liver cancer is thought to result from the exposure to many risk factors.

• Risk factors vary from one place to another, depending on habits, lifestyle, food consumed and surrounding infections.

• Prevention of liver cancer requires knowledge of these risk factors and ways to avoid them

Risk factors in Africa

Major risk

• 78% due to viral hepatitis (WHO)

• HBV …..50-80% (G)C

• HCV …..10- 25%

• Aflatoxin B1 (sub/ Saharan Africa)

• Dietary iron overload (sub/ Saharan Africa)

Minor risk

• Alcohol

• Obesity /NAFLD/DM

Bahri O et al, World J Hepatol,2011Kew MC,2013

Africa Liver Cancer Consortium

• HBV is the main cause .

• Over 50 – 60% in SSA are HBsAg+

• Another 20 -50 % have previous chronic B or occult HBV infection

• 43% of HBV –related HCC developed in adults younger than 40 y (32.5-37.5ys

• HCV is important cause in north Africa (Egypt)

• HCV –related cases occurred later after 50 ys with a peak between 57.5-62.5 ys

Africa Liver Cancer Consortium

Africa Liver Cancer Consortium

Surveillance of HCC

*Slightly lower (£30,000) or significantly higher levels (up to $150,000) have been proposed to account for inflation, specific national healthcare resources and other factorsEASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019

• High rate of HCC in certain risk groups makes surveillance a cost-effective route to reducing mortality

Recommendations

• Implementation of screening programmes to identify at-risk candidate populations should be improved

• Such programmes are a public health goal, aiming to decrease HCC-related and overall liver-related deaths

Low Strong

Patients at high risk of developing HCC should be entered into surveillanceprogrammes. Government health policy and research agencies should address these needs

Moderate Strong

Level of evidence Grade of recommendation

Influenced by a number of factors• Incidence of HCC in target populations

• Availability of efficient diagnostic tests at acceptable costs

• Availability and effectiveness of treatments

Surveillance in patients at high risk of HCC

*Patients at low HCC risk left untreated for HBV and without regular 6-month surveillance must be reassessed at latest on a yearly basis to verify progression of HCC risk. †PAGE-B score is based on decade of age (16–29 = 0, 30–39 = 2, 40–49 = 4, 50–59 = 6, 60–69 = 8, ≥70=10), gender (M = 6, F = 0) and platelet count (≥200,000/µl = 0, 100,000–199,999µl = 1, <100,000 = 2): a total sum of ≤9 is considered at low risk of HCC (almost 0% HCC at 5 years) a score of 10–17 at intermediate risk (3% incidence HCC at 5 years) and ≥18 is at high risk (17% HCC at 5 years) EASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019

• Surveillance is recommended in specific target populations

• Interval should be dictated by rate of tumour growth and tumourincidence in target population

• 6-month interval is reasonable and cost-effective

Recommendations

• Cirrhotic patients, Child–Pugh stage A and B Low Strong

• Cirrhotic patients, Child–Pugh stage C awaiting LT Low Strong

• Non-cirrhotic HBV patients at intermediate or high risk of HCC* (according to PAGE-B† classes for Caucasian subjects, respectively 10−17 and ≥18 score points)

Low Weak

• Non-cirrhotic F3 patients, based on an individual risk assessment Low Weak

Level of evidence Grade of recommendation

Surveillance between East and West

Prevention

*Level of evidence high, grade of recommendation strongEASL CPG HCC. J Hepatol 2018; doi: 10.1016/j.jhep.2018.03.019

• Primary prevention of HCC can be achieved with universalvaccination against HBV

• Progression to cirrhosis and HCC can be prevented by:

• Antiviral treatment in patients with chronic hepatitis B and C*

• Adoption of healthy lifestyle measures

Recommendations

Vaccination against hepatitis B reduces the risk of HCC and isrecommended for all newborns and high-risk groups

High Strong

Governmental health agencies should implement policies that:• Prevent HBV/HCV transmission• Counteract chronic alcohol abuse• Promote lifestyles that prevent obesity and metabolic syndrome

Moderate Strong

In patients with chronic hepatitis, use antiviral therapies to: • Maintain HBV suppression in chronic hepatitis B• Maintain SVR in chronic hepatitis C

High Strong

Level of evidence Grade of recommendation

Prevention of HBV and HCV Avoid Aflatoxin B1 Avoid dietary Iron overl

HCC preventive interventions

HCC Surveillance programmes

Prevention Strategies in AfricaSustainable Development Goals

WHO strategies for non communicable disease and viral hepatitis

Primary prevention :

Elimination of viral hepatitis as a major health problem threat by 2030

o Mass treatment of HCV

o HBV immunization

o safe injection

o avoid parental treatment

Decrease aflatoxin exposure

Reducing Alcohol and tobacco

Control DM and obesity

Community and patient education programs

o risk factors for hepatitis

o Aflatoxin and associated liver disease

o health lifestyle options

Who : Global sector strategy on viral hepatitis 2016-2021Who : global action plan for the prevention and control of noncommunicable diseases 2013- 2020

HCV

• Prevention of HCV

• Egypt role model in mass treatment

• Impact of HCV treatment

Access to HCV Therapy

POLARIS OBSERVATORY

o Polaris Observatory, an initiative of the non-profit CDA Foundation, provides epidemiological data, modeling tools, training and decision analytics to support eliminating Hepatitis B and C globally by 2030.

o Offers the most up-to-date estimates for the hepatitis C virus (HCV), hepatitis B virus (HBV) disease burden and economic impact, and offers strategies for elimination of each virus, along with financing options.

Impact of HCV Treatment

Endorsement of Success

.

110000055%485000

24%

35000018%

450002%

250001%

2,005,000patients

governmentalsupport

HIO

Total number of treated patients

in Egypt

110000055%

48500024%

35000018%

450002%

250001%

2,005,000patients

governmental support

HIO

private

*Police & Army forces

Presidential initiative

Before mass screening initiative in 1st Oct 2018

Impact of HCV treatment

Waked I, et al. Arab J Gastroenterol 2014;15:45–52

2013

2020

a) Increase efficacy only

b) Increase efficacy and treatment

Treated (annual) 65,000 65,000 325,000

Treatment rate 1.1% 1.1% 7.1%

Average SVR 48% 90% (2014) 90%

Newly diagnosed (annual) 125,000 125,000 340,500

Common treatment age 15–59 15–59 15–74

Treated stages ≥ F2 ≥ F2 ≥ F0

6.000.000

4.045.000

280.000

0

1.000.000

2.000.000

3.000.000

4.000.000

5.000.000

6.000.000

7.000.000

Total infected

-95%

630.000

507.000

76.000

0

200.000

400.000

600.000

800.000

Compensated cirrhosis

-88%

16.000 16.000

2.400

0

10.000

20.000

HCC

-85%

138.000

110.000

17.000

0

50.000

100.000

150.000

Decompensated cirrhosis

-87%

2013

201320132013

2030a 2030b

2030a 2030b2030a 2030b2030a 2030b

HBV

• HBV vaccination

• Perinatal transmission prevention

• Antiviral treatment for HBV

HBV Vaccination

HBV Perinatal infection Transmission Prevention

Impact of HBV Treatment

HBV TreatmentPolaris Observatory

Prevention of HBV –related liver Fibrosis and cancer in Africa : The PROLIFICA study

• PROLIFICA

• PRevention Of LIver Fibrosis and Cancer in Africa

• Established in 2011 in three West African countries: Senegal, the Gambia and Nigeria

• This is an on-going five-year translational research project funded by the European Union Framework 7 (www.prolifica.eu; EU-FP7 #265994) .

• Aim of the project is to reduce the incidence of HBV- related HCC in West Africa :

The PROLIFICA study

PROLIFICA study design

• Consists of two platforms:

West African Treatment Cohort for HBV (WATCH)

and hepatocellular carcinoma case-control study (HC4).

The WATCH study has been conducted in two parts:

➢a population-based study, with 13,500 people screened for HBV infection using a point-of-care test in Senegal and The Gambia.

➢The second study is a non-randomised, open label study of tenofovir therapy for HBsAg positive patients who fulfilled EASL 2012 treatment guidelines for nucleoside analogue therapy

➢The HC4 study was designed to develop a research platform for discovering and validating biological markers of HCC in Nigeria, The Gambia and Senegal.

The PROLIFICA study

.

The data provided by PROLIFICA will be crucial for the development of local &

WHO guidelines

AflatoxinDistribution of HCC RELATED AFB1

Liu Y, enviro Health Perspect ,2010

• Accounts 40% of HCC

• Causes mutation of p53 gene

• Aflatoxin B1 and HBV have synergstic effect (RR 54.1 ) with dual exposure

• Decrease AFB1 below detectable limits will decrease HCC incidence in general population by 15 -19% and in HbsAg population by 10-29%.

Aflatoxin Prevention Strategy

Iqbal et al, food safety and security.2018Nieru RW,2014

adequate irrigation & use of fungicides

Sun-drying on cloth not groundRemoving mouldy cropsImprove storage facilities

HCC in Africa….what we need??? • HCC is a preventable disease ..Primary Prevention Strategy remains the most important with a

Public health approach on risky behaviours. Immunization of HBV at birth is critical

but remains poorly implemented in Africa.

• HCC could be curable ……….Establish a simple program for early detection will improve OS.

• Implement “Screen & treat” for HBV & HCV at low coast

• Develope adaptable resource –sensitive HCC Guidelines for Africa

• Develop centers of excellence in African countries (Improve diagnostic and curative methods.)

management

training

Clinical trials/ regestries

• Effective fight against aflatoxin and alcohol consumption..

Thank you

abdelazizashraf@hotmail.com